Halogenated thiopyridines



United States Patent ABSTRACT OF THE DISCLOSURE Halogenatedthiopyridines corresponding to the formula L-SR wherein R representshydrogen, alkali metal, alkyl, monohalolower alkyl, dihalolower alkyl,trihalolower alkyl, phenyl, monohalophenyl, benzyl and monohalo-benzyl,and L represents a r 11 Y p1 Y n N/ N/ or N I i 0013 01 Y z 01 wherein Xrepresents hydrogen or chorine, Y represents bromine, chlorine orfluorine and Z represents hydrogen or Y.

This application is a continuation-in-part of my 00- pendingapplication, Ser. No. 444,861, filed April 1, 1965, now Patent No.3,296,272 granted Jan. 3, 1967 which is a continuation-in-part ofapplication Ser. No. 417,837 fi ed Dec. 11, 1964 and now abandoned.

The novel compounds of the present invention are halogenatedthiopyridines having the formula In this and succeeding formulae, Rrepresents hydrogen, alkali metal, alkyl, monohalolower alkyl,dihalolower alkyl, trihalolower alkyl, phenyl, monohalophenyl, benzyl ormonohalobenzyl; and L represents one of the radicals f t r t f t N or Nl l l 0013 Cl Y Z Cl wherein X represents chlorine or hydrogen, each Yrepresents chlorine, bromine or fluorine, and Z represents Y orhydrogen.

The term alkali metal as employed in the present specification andclaims refers to sodium and potassium. The term alkyl as employed in thepresent specification and claims designates an alkyl group containing 1,2, 3, 4, and up to 12 carbon atoms, and from 1 to 2, to 3, to 4, to 5,to 6, and up to and including 12 carbon atoms such as dodecyl, octyl,heptyl, hexyl, sec.-hexyl, butyl, decyl, 4-methyldecyl, undecyl, nonyl,isobutyl, tert.-butyl, isoamyl, amyl, propyl, ethyl, isopropyl,3-ethylnonyl, Z-ethylhexyl, and 3-propylheptyl. The expression loweralkyl is employed in the present specification and claims to designatean alkyl group containing 1, 2, 3, 4, or carbon atoms, and from 1 to 2,to 3, to 4, to 5 carbon atoms such as methyl, ethyl, isopropyl, propyl,tert.-butyl, butyl, amyl, sec-amyl, etc. Also, the terms monohaloloweralkyl, dihalolower alkyl, trihalolower alkyl, halophenyl and halobenzylrepresent lower alkyl, phenyl or benzyl moieties substituted withbromine or chlorine. Representative halo-lower alkyl moieties includeomega-trihalo-loweralkyl; omega-dihaloloweralkyl, omeice ga-halo-loweralkyl; alpha-halo-loweralkyl; alpha-dihalolower alkyl;2,3-dihalo-propyl, butyl or amyl; 2,2,3-trihalopropyl, butyl or amyl;3,4-dihalobutyl; 3,4-dihaloamyl, 4,5-dihaloamyl; 2,3,4-trihalobutyl,3,4,4-trihalobutyl, etc.

For convenience those compounds of the invention wherein R is hydrogenare hereinafter called halopyridyl mercaptans; those compounds wherein Ris alkali metal are called halopyridyl mercaptan alkali metal salts; andall other compounds of the invention are called halopyridyl sulfides.

The new compounds of the present invention have been found to be usefulas pesticides for the control of various pests such as bacteria, fungi,nematodes, insects, crustaceans, and aquatic and terrestrial plants.Representative pests include root knot nematodes, cockroaches, confusedflour beetles, daphnia, crabgrass, salvinia, bean mildew, Candidapelliculosa, Pullularia pullulans, Staphylococcus aureus and potatoscab.

The new compounds of the present invention are prepared by a variety ofmethods. In those cases wherein R represents R and R is alkyl, phenyl,monohalo-phenyl, benzyl, or monohalo benzyl, an alkali metal mercaptansalt having the formula R'S-alkali metal The reaction proceeds readilyat temperatures of from 60 C. to C. With the production of the desiredhalopyridyl sulfide products and the alkali metal halide of reaction. Insuch a procedure, the reactants are intimately contacted together in aninert organic liquid as reaction medium. Representative inert organicliquids include ethanol, methanol, isopropanol, dimethylsulfoxide anddimethoxyethane. Water can also be employed as the reaction medium,however, the organic liquids are preferred. The reaction consumes thereactants in equimolar proportions and the use of substantiallyequimolar proportions is preferred. The use of the alkali metalmercaptan in molar amounts substantially in excess of the molar amountof halopyridine results in the formation of bis-thiosu-bstitutedcompounds with the attendant decrease in yield of the halopyridylsulfides of the present invention.

During or following the contacting of the reactants, the reactionmixture is maintained at a temperature within the reaction temperaturezone for several hours. In a convenient procedure, the reaction mixturecan be maintained at the reaction temperature until there is a cessationin the precipitation of the alkali metal halide of reaction. Followingthe reaction period the reaction mixture is filtered to remove thealkali metal halide of reaction and the filtrate thus obtainedconcentrated to induce the precipitation of the halopyridyl sulfideproduct and the precipitated product isolated by filtration, decantationor centrifugation. In alternate isolation procedures, the filteredreaction mixture is fractionally distilled to obtain the product as adistillation product or concentrated to dryness to obtain the product asa residue. In yet another isolation procedure, the reaction mixture ispoured into water whereupon the halopyridyl sulfide precipitates in theaqueous mixture and the precipitated product is then separated byfiltration, centrifugation or decantation.

Representative halopyridines employed as starting materials include:2,3,4,6-tetrachloropyridine, 2,6-dibromo-3,4,S-trichloropyridine, 2iluoro 3,4,5-trichloropyridine, Z-trichloromethyl3,4,5,6-tetrachloropyridine, Z-trichloromethyl-3,4,5-trichloropyridine,2-bromo-3,4,5- trichloropyridine, 2trichloromethyl-3,4,6-trichloropyridine,2-fiuoro-3,4,5,6-tetrachloropyridine, 2,6-difluoro-3,4,5-trichloropyridine, 2,3,4,5,6-pentachloropyridine and2-bromo-3,4,5,6-tetrachloropyridine. I In an alternative method for theproduction of these halopyridyl sulfides, the halopyridine compoundsemployed in the preceding method are reacted with alkali metal sulfideto prepare the mercaptan of the corresponding pyridines wherein themercapto group enters the 4-position on the pyridine nucleus. Thesemercaptans are thereafter reacted with a suitable halide (R'X) to obtainthe desired halopyridyl sulfides. Where it is desired to obtain thehalopyridyl sulfides wherein R represents R" and R" ismonohalolower-alkyl, dihaloloWer-alkyl or trihalolower-alkyl, themercaptans of the pyridines prepared as described above are reacted withan equimolar quantity of a suitable halo substituted material (R"X).

The reaction between the alkali metal sulfide and the halopyridine iscarried out at temperatures between 65 and 110 C. and preferably attemperatures between 80 and 100 C. The reaction of the halopyridylmercaptan alkali metal salt with the suitable halide generally proceedsreadily at temperatures of from 80 to 120 C. However, when halo-benzenesare being employed the reaction is carried out under pressure attemperatures of about 150 C. or greater. When R represents ahaloloweralkyl such as monohalolower alkyl, dihalolower alkyl ortrihalolower alkyl, the reaction proceeds readily at temperaturesbetween 60 and 120 C. In converting the halopyridine to the halopyridylmercaptan alkali metal salt, the reaction consumes the reactants inequimolar proportions and optimum yields are obtained by the use of suchproportions. However, slight excesses of alkali metal sulfides (aboutpercent) do not adversely affect the yields. Likewise, the conversion ofthe halopyridyl mercaptan-alkali metal salts to the correspondingsulfide derivatives consumes equimolar proportions of alkali metal saltand halide, and the use of such proportions is preferred. However, aslight excess (about 10 percent) of the halide, with respect to thehalopyridyl mercaptan alkali metal salts, can be employed withoutadversely affecting the yields. Representative alkali metal sulfidesemployed as starting materials include sodium sulfide and potassiumsulfide.

In carrying out the production of the halogenated thiopyridines of thepresent invention by this alternate method, the halopyridine and thealkali metal sulfide are admixed in any order or fashion in the presenceof an organic liquid as reaction medium. The temperature of the reactionmixture thus obtained is maintained in the reaction temperature zone fora few hours. At this point the halopyridyl mercaptan alkali metal saltcompounds of the present invention can be readily isolated from thereaction mixture by evaporation to dryness. However, in a convenientprocedure the halopyridyl mercaptan alkali metal salt is reacted in situwith suitable halide to produce the corresponding halopyridyl sulfide.In such a procedure, the suitable halide is added to the reactionmixture containing the halopyridyl mercaptan alkali metal salt and thereaction mixture thus obtained maintained at a temperature in thereaction temperature range for a few hours. Conveniently, reactionconditions are maintained until there is a substantial cessation in theprecipitation of the alkali metal halide of reaction. Following thereaction period, the desired halopyridyl sulfide product is separatedfrom the reaction mixture as previously described.

Alkali metal salts such as the sodium or potassium salts of thefollowing mercaptans are reacted with a suitable halide to obtain thehalopyridyl sulfide products of the present invention:2,3,6-trichloro-4-pyridyl mer captan, 2,3,5,6-trichloro-4-pyridylmercaptan, Z-trichloromethyl-3,5,6-trichloro-4-pyridyl mercaptan,2,3,5,6-tetrachloro-4-pyridyl mercaptan, 2,6-difluoro-3,4-dichloro-4pyridyl mercaptan, 2,6-difluoro-3-chloro-4-pyridyl mercaptan,2-bromo-3,6-dichloro-4-pyridyl mercaptan, 2- bromo 3,5 dichloro -6fiuoro 4 pyridyl mercaptan, 2-bromo-3,5,6-trichloro-4-pyridyl mercaptan,and 2,6- dibromo-3,5-dichloro-4-pyridyl mercaptan.

The halopyridyl mercaptan alkali metal salts can be easily converted tothe corresponding halopyridyl mercaptan corresponding to the formula Insuch a procedure, the alkali metal salt is dispersed in an acid aqueousmedia whereupon the free SH compound will precipitate. The precipitatedproduct can be isolated by convenient procedures such as filtration,decantation or centrifugation.

In still another procedure, the halopyridine mercaptans are prepared -byreacting a halopyridine with sodium or potassium hydrosulfide. Thereaction is carried out under the same conditions as herein describedfor the production of the halopyridyl mercaptan alkali metal salts froma halopyridine and alkali metal sulfide.

The halopyridyl sulfide alkali metal salts can also be prepared byreacting sodium, potassium, sodium hydroxide or potassium hydroxide witha halopyridyl mercaptan corresponding to one of the formulas.

The reaction is carried out in an organic liquid as reaction medium andtakes place readily at temperatures between 25 and C. In a convenientprocedure, the reaction is carried out at the boiling temperature of thereaction mixture. The proportions of the reactants to be employed arenot critical, some of the desired product being formed upon contactingthe reactants in any proportions. However, the reaction consumes thereactants in equimolar proportions and the use of substantiallyequimolar proportions is preferred. In carrying out the production ofthe alkali metal salt compound the reactants are contacted in any orderor fashion in the liquid reaction medium. Following the contacting ofthe reactants the reaction mixture is maintained at a temperature withinthe reaction temperature range for a short period of time. Thereafter,the reaction mixture is subjected to evaporation to remove the lowboiling constituents and obtain the product as a solid or oily residue.

The following examples are merely illustrative and are not to beconstrued as limiting.

Example 1 Example 2 N SNa 7 Sodium (3.2 grams; 0.14 mole) was dissolvedin 175 milliliters of methanol. To the resulting methanol solution,2,3,5-trichloro-4-pyridyl mercaptan (30.0 grams; 0.14 mole) was addedwith stirring and the resulting solution heated at the boilingtemperature and under reflux for three hours. Following the heatingperiod, the reaction mixture was subjected to evaporation in vacuo toobtain a crystalline solid residue. This crystalline solid residue wasfound to melt at 250 C. and infrared analysis confirmed the identity ofthe crystalline solid residue as being 2,3,5-trichloro-4-pyridylmercaptan sodium salt.

Example 3 2,3,5-trichloro-4-pyridyl mercaptan sodium salt grams; 0.0423mole) was dissolved in 50 milliliters of dimethoxyethane. To thesolution thus prepared 1,2-dibromoethane (15.9 grams; 0.0846 mole) wasadded, with stirring, slowly and portionwise over a period of two hours.During the addition of the 1,2-dibromoethane the reaction mixture wasmaintained at room temperature. Following the contacting of thereactants, the reaction mixture was filtered to remove the solid sodiumbromide which precipitated in the reaction mixture and the filtrate thusobtained was distilled to remove the low boiling constituents and obtaina dark residue. This liquid residue was then dispersed in hexane and thehexane mixture filtered to remove the undissolved solid. The hexanefiltrate was then cooled and the crystalline solid product whichprecipitated during the cooling procedure was separated by filtrationand saved. The filtrate thus obtained was evaporated to dryness toobtain additional crystalline solid product. The2-bromoethyl-2,3,5-trichloro-4-pyridyl sulfide product was found to meltat 43.5 C. (corrected) and to have carbon, hydrogen, bromine, chlorine,nitrogen and sulfur contents of 26.51, 1.63, 24.5, 32.8, 4.66 and 10.1percent, respectively, by analysis as compared to the theoreticalcontents of 26.10, 1.57, 24.80, 33.00, 4.36 and 9.98 percent,respectively.

Example 4 3,5 dichloro 2,4 difluoropyridine (10 grams; 0.0547 mole) wasdissolved in 30 milliliters of dimethoxyethane. Sodium (1.29 grams;0.0562 mole) was dissolved in 35 milliliters of ethanol and theresulting solution cooled to less than 10 C. and methyl mercaptan (2.8grams; 0.583 mole) added thereto. The ethanol solution containing thesodium methyl mercaptan was then added slowly dropwise over a period of25 minutes to the solution of dichloro difluoropyridine indimethoxyethane. Following the admixing of the reactants, the reactionmixture was heated to the reflux temperature and filtered to remove thesalt which had precipitated during the reaction. The filtrate thusobtained was subjected to evaporation in vacuo at 40 C. to remove thelow boiling constituents and obtain a residue. This residue was thendissolved in hot hexane and the hexane solution filtered to remove anysolid material. The filtered hexane solution was then distilled atatmospheric pressure at 100 C. to remove the low boiling constituentsand obtain a residual oil. The oilymethyl-3,5-dichloro-2-fluoro-4-pyridyl sulfide compound thus obtainedwas found to have carbon, hydrogen, chlorine, fluorine, nitrogen, andsulfur contents of 34.92, 2.08, 33.32, 9.76, 6.20 and 14.75 percent,respectively, as compared to the theoretical content of 34.14, 1.43,33.60, 9, 6.64. and 15.19, percent, respectively.

The following compounds of the present invention (M.P. and M.W.designate melting point and molecular weight, respectively) wereprepared in accordance with the methods herein set forth:

3,5-dichloro-2,-6-difluoro-4-pyridyl mercaptan, M.W. 2162,3,5,6-tetrachloro-4-pyridyl mercaptan, M.P.

157.5-160.5 C. 2,3,5-trichloro-4-pyridyl mercaptan, M.P. 67 C.2,3,5,6-tetrachloro-4-pyridyl mercaptan sodium salt,

M.W. 271.4 2,3,6-trichloro-4-pyridyl mercaptan, M.P. 80 C.

Benzyl 2,3,5,6-tetrachloro-4-pyridyl sulfide, M.W. 339.1

2-bromoethyl 2,3,5-trichloro-4-pyridyl sulfide, M.P.

5-bro:mopentyl-2,3,5-trichloro-4-pyridyl sulfide,

2-bromo-1-chloroethyl 2,3,5,6-tetrachloro-4-pyridyl sulfide, M.P. 685 C.

2-bromoethyl-2-3,5,6-tetrochloro-4-pyridyl sulfide,

M.P. 99 C.

see-Butyl 2,3,5 ,6-tetrochloro-4-pyridyl sulfide,

M.P. 40.5 C.

Butyl 2,3,5-trichloro-4-pyridyl sulfide, M.W. 270.6

Butyl 3,5-dichloro-2-(trichloromethyl)-4-pyridyl sulfide,

Butyl 3,5-dichloro-2,6-difluoro-4-pyridyl sulfide,

tert.-Butylthio 2,3,5-trichloro-4-pyridyl sulfide,

p-Chlorophenyl 3,5-dichloro-2-(trichloromethyl)-4- pyridyl sulfide, M.W.408.0

Ethyl 3,5-dichloro-2-(trichloromethyl) -4-pyridyl sulfide,

3,S-dichloro-Z-(trichloromethyl)-4-pyridyl mercaptan,

M.P. 132-134 C.

Octyl 3,5-dichloro-2-(trichloromethyl)-4-pyridyl sulfide,

Methyl 3,5-dichloro-2-(trichloromethyl)-4-pyridyl sulfide,

M.P. 7476 C.

2-chloroethyl 2,3,5,6-tetrachloro-4-pyridyl sulfide,

M.P. 995 C.

Chloromethyl 2,3,5,6-tetrachloro-4-pyridyl sulfide,

M.P. 89-91 C.

3-chloropropyl 2,3,5 ,6-tetrochloro-4-pyridyl sulfide,

M.P. 61 C.

' Isopropyl 2,3,5,6-tetrachloro-4-pyridyl sulfide,

M.P. 42 C. Hexyl 2,3,5,6-tetrachloro-4-pyridyl sulfide, M.P. 35.5 C.Isobutyl 2,3,5,6-tetrachloro-4-pyridyl sulfide, M.W. 305.1 Phenyl 2,3,5,6-tetrach'loro-4-pyridyl sulfide, M.P. 91.5 C. Propyl2,3,5,6-tetrachloro-4-pyridyl sulfide, M.P. 41.0 C. 2-chloroethyl2,3,5-trichloro-4-pyridyl sulfide, M.P. 37 C. Chloromethyl2,3,5-trichloro-4-pyridyl sulfide, M.W. 263 p-Chlorophenyl2,3,5-trichloro-4-pyridy1 sulfide, M.P. 118 C. Isopropyl 2,3 ,5-trichloro-2- (trichloromethyl) -4-pyridyl sulfide, M.W. 378 Methyl2,3,6-trichloro-4pyridyl sulfide, M.P. 113 C. Methyl2,3,5-trichloro-6-(trichloromethyl)-4-pyridyl sulfide, M.P. 5759 C.Methyl 2,3,5-trichloro-4-pyridyl sulfide, M.P. 41.2 C.

The com ounds of the present invention are useful as pesticides for thecontrol of various bacteria, fungi, nematodes, insects, crustaceans andaquatic and terrestrial plants. For such use, the unmodified compoundcan be employed. Alternatively, the compound can be dispersed on aninert finely divided solid and the resulting preparation employed as adust. Also, such compounds or dust compositions containing said compoundcan be dispersed in water with or without the aid of additional wettingagents and the resulting aqueous dispersions employed as sprays. Inother procedures, the compounds can be employed as solutions inpetroleum distillates or in other solvents or as a constituent ofoil-in-water or water-inoil emulsions. Such liquid compositions can beemployed as sprays, drenches, or washes.

In representative operations pentyl 2,3,5,6-tetrachloro- 4-pyridylsulfide and hexyl 2,3,5,6-tetrachloro4-pyridyl sulfide each whenemployed as the sole toxic constituent in liquid compositions which areapplied to plots of weeds in amounts sufiicient to provide 20 pounds oftoxicant per acre gave complete kills of pig weeds. In other operations,methyl 2-3-5 trichloro-6-(trichloromethyl)-4- pyridyl sulfide givescomplete kills of cotton leaf perforator (Buccultltrix thurberiella)when employed as the sole toxicant constituent in liquid compositionsand in an amount suflicient to provide the toxicant at a dosage of 30pounds per acre.

In still further representative operations phenyl 2,3,5,6-tetrach-loro-4pyridyl sulfide when employed as the sole toxicantconstituent in aqueous compositions and at a concentration of 100 partsper million by weight of the composition gave complete kills and controlof bactn'umfire blight (Erwinz'a amylovora), rice blast, Basillus cereusand Trichlophyzon mentagrophytes when applied to viable growingmicroorganisms.

The halopyridyl sulfides of the present invention are useful asintermediates for the preparation of new pyridyl sulfones and sulfoxidesclaimed in my copending application Ser. No. 444,861 filed Apr. 1, 1965.In such operations the halopyridyl sulfides are oxidized by conventionalprocedures to produce the corresponding pyridyl sulfones or sulfoxides.These pyridyl sulfones and pyridyl sulfoxides are useful as pesticidesfor the kill and control of various pests such as fungi and bacteria.

I claim:

1. A halogenated thiopyridine compound corresponding to the formula LSRwherein R represents hydrogen, alkali metal, alkyl of from 1-12 carbonatoms, monohalolower, alkyl, dih-alodower alkyl, trihalolower alkyl,phenyl, monohalophenyl, benzyl or monohalobenzyl and L represents one ofthe formulas in which X represents hydrogen or chlorine, Y representsbromine, chlorine or fluorine and Z represents hydrogen or Y.

2. The halogenated thiopyridine claimed in claim 1 wherein the compoundis methyl 2,3,5,6-tetrach1oropyridine-4-pyridyl sulfide.

3. The halogenated thiopyridine claimed in claim 1 wherein the compoundis methyl 2,3,5-trichloro-4-pyridyl sulfide.

4. The halogenated thiopyridine claimed in claim 1 wherein the compoundis 2,3,5,6-tetrachloro-4-pyridyl mercaptan sodium salt.

5. The halogenated thiopyridine claimed in claim 1 wherein the compoundis 2,3,5-trichloro-4-pyridyl mercaptan sodium salt.

6. The halogenated thiopyridine claimed in claim 1 wherein the compoundis 2,3,5,6-tetrachloro-4-pyridyl sulfide.

7. The halogenated thiopyridine claimed in claim 1 wherein the compoundis chloromethyl 2,3,5,6-tetrachloro- 4-pyridyl sulfide.

References Cited UNITED STATES PATENTS 2,826,584 3/1958 Cislak260--294.8

JOHN D. RANDOLPH, Primary Examiner.

A. ROTMAN, Assistant Examiner.

Disclaimer 3,364,223.Howa1'd Johnston, Walnut Creek, Calif. HALOGENATEDTHI- OPYRIDINES. Patent dated J an. 16, 1968. Disclaimer filed Oct. 20,1972, by the assignee, The Dow Chemical Company. Hereby enters thisdisclaimer to claim 1 of said patent.

[Ofiicial Gazette January 30, 1973.]

